Samuel J. Hassenbusch

Polyanalgesic consensus conference 2007: recommendations for the management of pain by intrathecal (intraspinal) drug delivery: report of an interdisciplinary expert panel.

Background.  Expert panels of physicians and nonphysicians in the field of intrathecal therapies convened in 2000 and 2003 to make recommendations for the rational use of intrathecal analgesics based on the preclinical and clinical literature known up to those times. An expert panel of physicians convened in 2007 to update previous recommendations and to form guidelines for the rational use of intrathecal opioid and nonopioid agents.

An Updated Interdisciplinary Clinical Pathway for CRPS: Report of an Expert Panel

Abstract: The goal of treatment in patients with complex regional pain syndrome (CRPS) is to improve function, relieve pain, and achieve remission. Current guidelines recommend interdisciplinary management, emphasizing 3 core treatment elements: pain management, rehabilitation, and psychological therapy. Although the best therapeutic regimen or the ideal progression through these modalities has not yet been established, increasing evidence suggests that some cases are refractory to conservative measures and require flexible application of the various treatments as well as earlier consideration of interventions such as spinal cord stimulation (SCS). While existing treatment guidelines have attempted to address the comprehensive management of CRPS, all fail to provide guidance for contingent management in response to a sudden change in the patients medical status. This paper reviews the current pathophysiology as it is known, reviews the purported treatments, and provides a modified clinical pathway (guideline) that attempts to expand the scope of previous guidelines.

Evidence-Based Review of the Literature on Intrathecal Delivery of Pain Medication

Evidence-based medicine depends on the existence of controlled clinical trials that establish the safety and efficacy of specific therapeutic techniques. Many interventions in clinical practice have achieved widespread acceptance despite little evidence to support them in the scientific literature; the critical appraisal of these interventions based on accumulating experience is a goal of medicine. To clarify the current state of knowledge concerning the use of various drugs for intraspinal infusion in pain management, an expert panel conducted a thorough review of the published literature. The exhaustive review included 5 different groups of compounds, with morphine and bupivacaine yielding the most citations in the literature. The need for additional large published controlled studies was highlighted by this review, especially for promising agents that have been shown to be safe and efficacious in recent clinical studies.

Clinical guidelines for intraspinal infusion: Report of an expert panel

Consensus guidelines developed by an expert panel are helpful to clinicians when there is variation in practice and lack of a firm evidence base for an intervention, such as intraspinal therapy for pain. An internet-based survey of practitioners revealed remarkable variation in practice patterns surrounding intraspinal therapy. This prompted an interdisciplinary panel with extensive clinical experience in intraspinal infusion therapy to evaluate the results of the survey, the systematic reviews of the literature pertaining to this approach, and their own clinical experience with long-term spinal infusions. The panel proposed a scheme for the selection of drugs and doses for intraspinal therapy, and suggested guidelines for administration that would increase the likelihood of a successful outcome. These expert panel guidelines were designed to provide an initial structure for clinical decision making that is based on the best available evidence and the perspectives of experienced clinicians.

Long-term intraspinal infusions of opioids in the treatment of neuropathic pain

Long-term intraspinal infusions of opioid drugs are being increasingly utilized in patients with noncancer pain. Despite this, there is a lack of long-term information, including success and failure rates for pain relief and technical problems. During a 5-year period, 18 noncancer patients underwent implantation of programmable infusion pumps for long-term intrathecal opioid infusion. Patients had (a) neuropathic pain, (b) had failed or been ineligible for noninvasive treatments, and (c) obtained greater than 50% pain relief with intrathecal trial infusions of morphine sulfate or sufentanil citrate. A disinterested third-party reviewer evaluated patients at the most recent follow-up. Sixty-one percent (11/18) of patients had good or fair pain relief with mean follow-up 2.4 +/- 0.3 years (0.8-4.7 years). Average numeric pain scores decreased by 39% +/- 4.3%. Five of the 11 responders required lower opioid doses (12-24 mg/day morphine) and the remaining six patients required higher opioid doses (> 34 mg/day morphine). Failure of long-term pain relief occurred in 39% (7/18) despite good pain relief in trial infusions and the use of both morphine and sufentanil. Technical problems developed in 6/18 patients but appeared to be preventable with further experience. Long-term intrathecal opioid infusions can be effective in treatment of neuropathic pain but might require higher infusion doses.

Current practices in intraspinal therapy: A survey of clinical trends and decision making

Practice patterns were assessed via an internet-based survey distributed to physicians who manage implantable infusion pumps for pain management. Respondents consisted of 413 physicians who represented management of 13,342 patients, predominantly in the U.S. The survey used a standard questionnaire format plus two clinical vignettes to assess decision-making practices. The responding physicians chose morphine most often, but many other drugs were selected without clear indications. There was evidence of wide variations in clinical practice among physicians who use this modality. These findings highlight the need for practice guidelines based on research outcomes and expert experience to establish pathways for optimal management.

A pilot study of neurocognitive function in patients with one to three new brain metastases initially treated with stereotactic radiosurgery alone

OBJECTIVEWhether to administer or omit adjuvant whole-brain radiation therapy in conjunction with stereotactic radiosurgery (SRS) in the initial management of patients with one to three newly diagnosed brain metastases is the subject of debate. This report provides data from a pilot study in which neurocognitive function (NCF) was prospectively measured for patients with one to three newly diagnosed brain metastases treated with initial SRS alone. METHODSFifteen patients were prospectively treated with initial SRS alone. Assessment of NCF and magnetic resonance imaging scans were performed. RESULTSAt baseline, 67% of the patients had impairment on one or more tests of NCF. The domains most frequently impaired at baseline were executive function, motor dexterity, and learning/memory with an incidence of 50, 40, and 27% respectively. Brain metastasis volume (.3 cm3) measured at the time of initial SRS treatment was associated with worse performance on a measure of attention (P < 0.05). At 1 month, declines in the learning/memory and motor dexterity domains were most common. In a subgroup of five patients still alive 200 days after enrollment, four patients (80%) demonstrated stable or improved learning/memory, three (60%) demonstrated stable or improved executive function, and three (60%) demonstrated stable or improved motor dexterity relative to their baseline evaluation. CONCLUSIONAlthough two-thirds of the brain metastasis patients had impaired NCF at baseline, the majority of five long-term survivors had stable or improved NCF performance across executive function, learning/memory, and motor dexterity.

Outcome Variation among “Radioresistant” Brain Metastases Treated with Stereotactic Radiosurgery

OBJECTIVE:To determine the influence of histopathological diagnosis on the outcome of “radioresistant” brain metastases treated with stereotactic radiosurgery (SRS). METHODS:Patients (n = 189) with “radioresistant” brain metastases (n = 264) were consecutively treated with SRS between August 1991 and July 2002. The primary site of brain metastases was melanoma (n = 103), renal cell carcinoma (n = 77), and sarcoma (n = 9). The median age of the patients was 52 years, and the median Karnofsky Performance Scale score was 80. Initial brain metastasis presentation was single in 112 patients (59%). The median SRS dose was 18 Gy (range, 10–24 Gy). The median tumor volume was 1.6 cm3 (range, 0.06–27.5 cm3). The median follow-up of all patients was 7.4 months (range, 0.16–52 mo). RESULTS:The actuarial freedom from progression after 1 year was 64% for renal cell carcinoma patients, 47% for melanoma patients, and 0% for sarcoma patients (P < 0.001). The median survival time for all patients from time of SRS was 7.5 months. The rate of 1-year survival was 40% for renal cell carcinoma patients, 25% for melanoma patients, and 22% for sarcoma patients (P = 0.0354). The incidence of neurological death was lower among patients diagnosed with renal cell carcinoma (31%) than among patients with melanoma (66%) or sarcoma (60%) (P = 0.001). CONCLUSION:Survival after SRS is significantly worse for patients with melanoma and sarcoma brain metastases compared with patients with renal cell carcinoma. Our data show that progressive brain metastases seem to cause most of the cancer-related deaths among patients with SRS-treated melanoma and sarcoma brain metastases. Future investigations using chemotherapy or novel agents to enhance the effectiveness of SRS to melanoma and sarcoma brain metastases seem warranted.

Immunological responses in a patient with glioblastoma multiforme treated with sequential courses of temozolomide and immunotherapy: Case study

Cytotoxic chemotherapy that induces lymphopenia is predicted to ablate the benefits of active antitumor immunization. Temozolomide is an effective chemotherapeutic agent for patients with glioblastoma multiforme, but it induces significant lymphopenia. Although there is monthly fluctuation of the white blood cell count, specifically the CD4 and CD8 counts, there was no cumulative decline in the patient described in this case report. Depriving patients of this agent, in order to treat with immunotherapy, is controversial. Despite conventional dogma, we demonstrated that chemotherapy and immunotherapy can be delivered concurrently without negating the effects of immunotherapy. In fact, the temozolomide-induced lymphopenia may prove to be synergistic with a peptide vaccine secondary to inhibition of regulatory T cells or their delayed recovery.

Nonsmall cell lung cancer presenting with synchronous solitary brain metastasis

Solitary brain metastases occur in about 50% of patients with brain metastases from nonsmall cell lung cancer (NSCLC). The standard of care is surgical resection of solitary brain metastases, or stereotactic radiosurgery (SRS) plus whole brain radiation therapy (WBRT). However, the optimal treatment for the primary site of newly diagnosed NSCLC with a solitary brain metastasis is not well defined. The goal was to distinguish which patients might benefit from aggressive treatment of their lung primary in patients whose solitary brain metastasis was treated with surgery or SRS.